Terpinolene is found in a wide variety of plants and spices, including nutmeg, parsnips, cardamom, apples, cumin, and lilacs. The aroma profile of this terpene reflects this variety and can be described as a mix of floral, woodsy, sweet, and herbaceous. Due to its ‘fresh’ aroma, terpinolene is often used as an additive in cosmetic and household cleaning products. Several studies have investigated the effects of this terpene using essential oils (most notably tea tree oil) that are rich in terpinolene. Results suggest that this terpene may provide antioxidant[1]^,[2] and anti-bacterial[3] properties. In addition, animal models have demonstrated potential sedative[4] effects of this terpene, as well as a potential to treat pain, inflammation[5], and cancer[6].

[1] J Grassmann, S Hippeli, R Spitzenberger, E F Esltner. The monoterpene terpinolene from the oil of Pinus mugo L. in concert with alpha-tocopherol and beta-carotene effectively prevents oxidation of LDL. Phytomedicine 2005 Jun;12(6-7):416-23. doi: 10.1016/j.phymed.2003.10.005

[2] Kim HJ, Chen F, Wu C, Wang X, Chung HY, Jin Z. Evaluation of antioxidant activity of Australian tea tree (Melaleuca alternifolia) oil and its components. J Agric Food Chem. 2004 May 19;52(10):2849-54. doi: 10.1021/jf035377d. PMID: 15137824.

[3] Mazandarani, M. & Mirdeilami, Z. & Pessarakli, Mohammad. (2013). Essential oil composition and antibacterial activity of Achillea millefolium L. from different regions in North east of Iran. J. Med. Plants Res.. 7. 1063-1069.

[4] Ken Ito, Michiho Ito. The sedative effect of inhaled terpinolene in mice and its structure-activity relationships. Journal of Natural Medicines 2013 Oct;67(4):833-7. DOI: 10.1007/s11418-012-0732-1. Epub 2013 Jan 22.

[5] Macedo, E. et al. “Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation.” Brazilian Journal of Medical and Biological Research 49.7, DOI:10.1590/1414-431×20165103 (2016)

[6] Leanur Aydin, Hasan Turkez, Sener Tasdemir. Anticancer and antioxidant properties of terpinolene in rat brain cells. Arh Hig Rada Toksikol. 2013 Sep;64(3):415-24. DOI: 10.2478/10004-1254-64-2013-2365.

Pinene is unique in that it has two main isomers, alpha and beta, that are both common in the cannabis plant. These isomers have the same molecular composition but different arrangements and are usually notated as α-pinene and β-pinene. As its name suggests, this terpene has a piney aroma and is abundant in most conifers. Pinene can be found in a large variety of plants, including rosemary, parsley, dill and—not surprisingly—pine trees! Various animal studies have demonstrated that pinene may exhibit gastroprotective[1], anxiolytic[2], and anticonvulsant[3] properties, as well as the potential to improve sleep quality[4]. In addition, some animal and in vitro studies have implicated this terpene as a potential treatment for various neurodegenerative diseases[5], including Alzheimer’s[6] and Parkinson’s Disease[7], due to its neuroprotective properties[8]. In vitro research, including studies on essential oils rich in pinene, has shown that pinene may display antioxidant[9], anti-inflammatory[10], and antimicrobial[11] effects. Finally, as with several other terpenes, pinene has been linked to anti-tumor[12] and anti-cancer[13] activity.

[1] Pinheiro Mde A, Magalhães RM, Torres DM, Cavalcante RC, Mota FS, Oliveira Coelho EM, Moreira HP, Lima GC, Araújo PC, Cardoso JH, de Souza AN, Diniz LR. Gastroprotective effect of alpha-pinene and its correlation with antiulcerogenic activity of essential oils obtained from Hyptis species. Pharmacogn Mag. 2015 Jan-Mar;11(41):123-30. doi: 10.4103/0973-1296.149725. PMID: 25709221; PMCID: PMC4329611.

[2] Kasuya H, Okada N, Kubohara M, Satou T, Masuo Y, Koike K. Expression of BDNF and TH mRNA in the brain following inhaled administration of α-pinene. Phytother Res. 2015 Jan;29(1):43-7. doi: 10.1002/ptr.5224. Epub 2014 Sep 17. PMID: 25230317.

[3] Felipe CFB, Albuquerque AMS, de Pontes JLX, de Melo JÍV, Rodrigues TCML, de Sousa AMP, Monteiro ÁB, Ribeiro AEDS, Lopes JP, de Menezes IRA, de Almeida RN. Comparative study of alpha- and beta-pinene effect on PTZ-induced convulsions in mice. Fundam Clin Pharmacol. 2019 Apr;33(2):181-190. doi: 10.1111/fcp.12416. Epub 2018 Oct 25. PMID: 30230028.

[4] Yang H, Woo J, Pae AN, Um MY, Cho NC, Park KD, Yoon M, Kim J, Lee CJ, Cho S. α-Pinene, a Major Constituent of Pine Tree Oils, Enhances Non-Rapid Eye Movement Sleep in Mice through GABAA-benzodiazepine Receptors. Mol Pharmacol. 2016 Nov;90(5):530-539. doi: 10.1124/mol.116.105080. Epub 2016 Aug 29. PMID: 27573669.

[5] Porres-Martínez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP. In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z Naturforsch C J Biosci. 2016;71(7-8):191-9. doi: 10.1515/znc-2014-4135. PMID: 27352445.

[6] Lee GY, Lee C, Park GH, Jang JH. Amelioration of Scopolamine-Induced Learning and Memory Impairment by α-Pinene in C57BL/6 Mice. Evid Based Complement Alternat Med. 2017;2017:4926815. doi: 10.1155/2017/4926815. Epub 2017 Nov 1. PMID: 29234406; PMCID: PMC5687139.

[7] Srivastava R, Choudhury PK, Dev SK, Rathore V. Neuroprotective effect of α-pinene self-emulsifying nanoformulation against 6-OHDA induced neurotoxicity on human SH-SY5Y cells and its in vivo validation for anti-Parkinson’s effect. J Biochem Mol Toxicol. 2021 Nov;35(11):e22902. doi: 10.1002/jbt.22902. Epub 2021 Aug 31. PMID: 34464010.

[8] Khoshnazar M, Parvardeh S, Bigdeli MR. Alpha-pinene exerts neuroprotective effects via anti-inflammatory and anti-apoptotic mechanisms in a rat model of focal cerebral ischemia-reperfusion. J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104977. doi: 10.1016/j.jstrokecerebrovasdis.2020.104977. Epub 2020 Jun 13. PMID: 32689608.

[9] Porres-Martínez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP. In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z Naturforsch C J Biosci. 2016;71(7-8):191-9. doi: 10.1515/znc-2014-4135. PMID: 27352445.

[10] Rufino AT, Ribeiro M, Judas F, Salgueiro L, Lopes MC, Cavaleiro C, Mendes AF. Anti-inflammatory and chondroprotective activity of (+)-α-pinene: structural and enantiomeric selectivity. J Nat Prod. 2014 Feb 28;77(2):264-9. doi: 10.1021/np400828x. Epub 2014 Jan 23. PMID: 24455984.

[11] Rodrigues KA, Amorim LV, Dias CN, Moraes DF, Carneiro SM, Carvalho FA. Syzygium cumini (L.) Skeels essential oil and its major constituent α-pinene exhibit anti-Leishmania activity through immunomodulation in vitro. J Ethnopharmacol. 2015 Feb 3;160:32-40. doi: 10.1016/j.jep.2014.11.024. Epub 2014 Nov 25. PMID: 25460590.

[12] Chen W, Liu Y, Li M, Mao J, Zhang L, Huang R, Jin X, Ye L. Anti-tumor effect of α-pinene on human hepatoma cell lines through inducing G2/M cell cycle arrest. J Pharmacol Sci. 2015 Mar;127(3):332-8. doi: 10.1016/j.jphs.2015.01.008. Epub 2015 Feb 7. PMID: 25837931.

[13] Jo H, Cha B, Kim H, Brito S, Kwak BM, Kim ST, Bin BH, Lee MG. α-Pinene Enhances the Anticancer Activity of Natural Killer Cells via ERK/AKT Pathway. Int J Mol Sci. 2021 Jan 11;22(2):656. doi: 10.3390/ijms22020656. PMID: 33440866; PMCID: PMC7826552.

As one of the most common terpenes present in the cannabis plant, abundant levels of myrcene can be found in cultivars from around the world. Often used as an additive in food manufacturing, myrcene can be found naturally in mangos, lemongrass, and bay leaves. Various studies on animal models have shown some promising applications for this terpene, including sedation[1], muscle relaxation[2], anti-inflammation[3], and overall pain relief[4]. Analyses of essential oils high in myrcene content have also indicated the possible antioxidant[5] and anti-ulcer[6] properties of this terpene. Furthermore, research on mouse models has demonstrated the potential of this terpene to treat ischemic stroke, due to its neuro[7] and cardiac[8] protective effects.

[1] 78. Freitas JC, Presgrave OA, Fingola FF, Menezes MA, Paumgartten FJ. Effect of beta-myrcene on pentobarbital sleeping time. Braz J Med Biol Res. (1993) 26:519–23. [PubMed] [Google Scholar] [Ref list]

[2] do Vale TG, Furtado EC, Santos JG Jr, Viana GS. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown. Phytomedicine. 2002 Dec;9(8):709-14. doi: 10.1078/094471102321621304. PMID: 12587690.

[3] McDougall, J.J.; McKenna, M.K. Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis. Int. J. Mol. Sci. 2022, 23, 7891. https://doi.org/10.3390/ijms23147891

[4] Paula-Freire LI, Molska GR, Andersen ML, Carlini EL. Ocimum gratissimum Essential Oil and Its Isolated Compounds (Eugenol and Myrcene) Reduce Neuropathic Pain in Mice. Planta Med. 2016 Feb;82(3):211-6. doi: 10.1055/s-0035-1558165. Epub 2015 Nov 19. PMID: 26584457.

[5] Ojeda, Adriana & Van Baren, Catalina & Elechosa, Miguel & Juárez, Miguel & Moreno, Silvia. (2013). New insights into antibacterial and antioxidant activities of rosemary essential oils and their main components. Food Control. 31. 189–195. 10.1016/j.foodcont.2012.09.022.

[6] Bonamin F, Moraes TM, Dos Santos RC, Kushima H, Faria FM, Silva MA, Junior IV, Nogueira L, Bauab TM, Souza Brito AR, da Rocha LR, Hiruma-Lima CA. The effect of a minor constituent of essential oil from Citrus aurantium: the role of β-myrcene in preventing peptic ulcer disease. Chem Biol Interact. 2014 Apr 5;212:11-9. doi: 10.1016/j.cbi.2014.01.009. Epub 2014 Jan 27. PMID: 24480520.

[7] Ciftci O, Oztanir MN, Cetin A. Neuroprotective effects of β-myrcene following global cerebral ischemia/reperfusion-mediated oxidative and neuronal damage in a C57BL/J6 mouse. Neurochem Res. 2014 Sep;39(9):1717-23. doi: 10.1007/s11064-014-1365-4. Epub 2014 Jun 28. PMID: 24972849.

[8] Burcu GB, Osman C, Aslı C, Namik OM, Neşe BT. The protective cardiac effects of Β-myrcene after global cerebral ıschemia/reperfusion in C57BL/J6 mouse. Acta Cir Bras. 2016 Jul;31(7):456-62. doi: 10.1590/S0102-865020160070000005. PMID: 27487280.

Previously known as α-caryophyllene, humulene is an isomer of the more commonly known terpene, β-caryophyllene. Not only do these terpenes share a similar molecular composition, but they also create similar earthy, peppery aromas and are often found together in nature. Some in vitro studies have shown that humulene may act as an anti-cancer agent[1], perhaps potentiated with the presence of β-caryophyllene[2]. Using essential oils rich in humulene, researchers have been able to demonstrate the potential anti-inflammatory[3] and antibacterial[4] effects of this terpene. Another study, using mouse models, concluded that humulene may also be able to treat allergic asthmatic airway inflammation[5]. While Humulene is also often invoked as an appetite suppressant, research supporting this claim is limited and further investigation is needed.

[1] Chen H, Yuan J, Hao J, Wen Y, Lv Y, Chen L, Yang X. α-Humulene inhibits hepatocellular carcinoma cell proliferation and induces apoptosis through the inhibition of Akt signaling. Food Chem Toxicol. 2019 Dec;134:110830. doi: 10.1016/j.fct.2019.110830. Epub 2019 Sep 25. PMID: 31562948.

[2] Legault J, Pichette A. Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel. J Pharm Pharmacol. 2007 Dec;59(12):1643-7. doi: 10.1211/jpp.59.12.0005. PMID: 18053325.

[3] Fernandes ES, Passos GF, Medeiros R, da Cunha FM, Ferreira J, Campos MM, Pianowski LF, Calixto JB. Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur J Pharmacol. 2007 Aug 27;569(3):228-36. doi: 10.1016/j.ejphar.2007.04.059. Epub 2007 May 22. PMID: 17559833.

[4] Pichette A, Larouche PL, Lebrun M, Legault J. Composition and antibacterial activity of Abies balsamea essential oil. Phytother Res. 2006 May;20(5):371-3. doi: 10.1002/ptr.1863. PMID: 16619365.

[5] Rogerio AP, Andrade EL, Leite DF, Figueiredo CP, Calixto JB. Preventive and therapeutic anti-inflammatory properties of the sesquiterpene alpha-humulene in experimental airways allergic inflammation. Br J Pharmacol. 2009 Oct;158(4):1074-87. doi: 10.1111/j.1476-5381.2009.00177.x. Epub 2009 May 8. PMID: 19438512; PMCID: PMC2785529.

Caryophyllene (also known as β-Caryophyllene or BCP) is a terpene found in several common herbs and spices like cloves, black pepper, cinnamon, basil, and oregano. In cannabis, caryophyllene often contributes to a peppery, earthy flavor profile. Animal models have demonstrated a possible interaction of caryophyllene with the endocannabinoid system[1] as well as pain relief via CB2 activation[2]. Other animal studies have identified this terpene as a potential treatment for several conditions, including anxiety[3], depression[4], inflammation[5], and overall pain relief[6]. In addition, in vitro studies have evaluated the antioxidant[7] and sedative[8] effects of this terpene. Finally—and perhaps most noteworthy—both in vitro[9] and animal[10] studies have implicated caryophyllene as a potential treatment for cancer, with human trials demonstrating its potential to treat nausea[11].

[1] Poddighe L, Carta G, Serra MP, Melis T, Boi M, Lisai S, Murru E, Muredda L, Collu M, Banni S, Quartu M. Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion. Lipids Health Dis. 2018 Feb 5;17(1):23. doi: 10.1186/s12944-018-0661-4. PMID: 29402275; PMCID: PMC5799897.

[2] Klauke AL, Racz I, Pradier B, Markert A, Zimmer AM, Gertsch J, Zimmer A. The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol. 2014 Apr;24(4):608-20. doi: 10.1016/j.euroneuro.2013.10.008. Epub 2013 Oct 22. PMID: 24210682.

[3] Bahi A, Al Mansouri S, Al Memari E, Al Ameri M, Nurulain SM, Ojha S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiol Behav. 2014 Aug;135:119-24. doi: 10.1016/j.physbeh.2014.06.003. Epub 2014 Jun 13. PMID: 24930711.

[4] Hwang ES, Kim HB, Lee S, Kim MJ, Kim KJ, Han G, Han SY, Lee EA, Yoon JH, Kim DO, Maeng S, Park JH. Antidepressant-like effects of β-caryophyllene on restraint plus stress-induced depression. Behav Brain Res. 2020 Feb 17;380:112439. doi: 10.1016/j.bbr.2019.112439. Epub 2019 Dec 17. PMID: 31862467.

[5] Gushiken LFS, Beserra FP, Hussni MF, Gonzaga MT, Ribeiro VP, de Souza PF, Campos JCL, Massaro TNC, Hussni CA, Takahira RK, Marcato PD, Bastos JK, Pellizzon CH. Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model. Oxid Med Cell Longev. 2022 Feb 3;2022:9004014. doi: 10.1155/2022/9004014. PMID: 35154574; PMCID: PMC8831077.

[6] Paula-Freire LI, Andersen ML, Gama VS, Molska GR, Carlini EL. The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice. Phytomedicine. 2014 Feb 15;21(3):356-62. doi: 10.1016/j.phymed.2013.08.006. Epub 2013 Sep 20. PMID: 24055516.

[7] Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK. Volatile constituents from Cinnamomum zeylanicum fruit stalks and their antioxidant activities. J Agric Food Chem. 2003 Jul 16;51(15):4344-8. doi: 10.1021/jf034169i. PMID: 12848508.

[8] Rabbani M, Sajjadi SE, Vaezi A. Evaluation of anxiolytic and sedative effect of essential oil and hydroalcoholic extract of Ocimum basilicum L. and chemical composition of its essential oil. Res Pharm Sci. 2015 Nov-Dec;10(6):535-43. PMID: 26779273; PMCID: PMC4698864.

[9] Mannino F, Pallio G, Corsaro R, Minutoli L, Altavilla D, Vermiglio G, Allegra A, Eid AH, Bitto A, Squadrito F, Irrera N. Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells. Cancers (Basel). 2021 Nov 16;13(22):5741. doi: 10.3390/cancers13225741. PMID: 34830893; PMCID: PMC8616110.

[10] Dahham SS, Tabana Y, Asif M, Ahmed M, Babu D, Hassan LE, Ahamed MBK, Sandai D, Barakat K, Siraki A, Majid AMSA. β-Caryophyllene Induces Apoptosis and Inhibits Angiogenesis in Colorectal Cancer Models. Int J Mol Sci. 2021 Sep 29;22(19):10550. doi: 10.3390/ijms221910550. PMID: 34638895; PMCID: PMC8508804.

[11] Shim, Hyun & Song, Dong & Shin, Cheol & Yoon, Hyuk & Park, Young & Kim, Nayoung & Lee, Dong. (2019). Inhibitory Effects of β-caryophyllene on Helicobacter pylori Infection: A Randomized Double-blind, Placebo-controlled Study. The Korean Journal of Gastroenterology. 74. 199. 10.4166/kjg.2019.74.4.199.